Worst-case simulations show effectiveness of cleaning closed systems in CNC environment, potential cost savings

BTEC scientist Haiwei Zhang conducts a bioburden reduction study.
BTEC scientist Haiwei Zhang conducts a bioburden reduction study by challenging a bioprocess skid with B. subtilis and cleaning the system with WFI at 80°C. Experiments were part of a three-year collaboration with BioPhorum.

Scientists at BTEC, in collaboration with the industry group BioPhorum, have helped prove the effectiveness of commonly used cleansers to reduce bioburden in functionally closed bioprocessing systems. According to BioPhorum, moving from inflexible operations in a grade C environment to a modern, flexible multi-product facility in a CNC environment will result in significant cost reductions. Capital costs may be reduced by as much as 45%, and even greater savings may be realized in operational costs, according to the group’s white paper about the project. BioPhorum, which has members from across the global biopharmaceutical industry, seeks to foster collaboration and accelerate the rate of progress within the industry.

From 2015 through 2018, BTEC collaborated with BioPhorum to carry out studies of bioburden reduction in hybrid (stainless steel and disposable) systems in a controlled-non-classified (CNC) environment. BTEC personnel conducted the experiments at the center’s facilities and collected data. The purpose of the study was to demonstrate that, for low bioburden processes, operating a functionally closed system in a CNC environment is equal to or better than operating an open process in a grade C environment. Closed systems offer manufacturers significant savings through the use of simpler facilities and reduced capital costs and operating expenses.

In the experiments at BTEC, a bioprocess test skid was challenged with known quantities of Bacillus subtilis and Micrococcus luteus using tri-clamp ferrule connections to simulate worst-case scenarios. Various cleansers typically found in the biopharmaceutical industry were then used to flush the skid. The residual bioburden was sampled from the process fluid and the ferrule connectors. At least a 3-log reduction of Micrococcus luteus was shown in all solutions that were tested. Log reductions for B. subtilus were between 0.4 and 4.4, with the best cleanser being 1 M NaOH, which provided 3.5-4.9 logs of reduction.

When BioPhorum published the results of this three-year project with BTEC, the group announced, “The study concluded that measures as simple as flushing with WFI may be successfully employed to effectively mitigate the risk of assembling and operating a modern hybrid [stainless steel and disposable] closed bioprocessing system in a controlled, non-classified environment. Over a five log reduction in bioburden was achieved with some cleaning agents.” The white paper detailing the studies is available for download from the organization’s website.

The collaboration between BioPhorum and BTEC was funded by BioPhorum member companies involved with its Closed Systems in CNC Space group. The goal of the group “is to provide data driven arguments and risk based approaches to support implementation of closed or functionally closed systems, and to operate those systems within CNC environments.” According to the group, such implementations offer the possibility of significant cost savings for industry, including reduced capital costs, lower operating costs, and increased energy conservation.

Posted 7/27/2018